Multiple sclerosis (MS) is considered to be a T cell mediated autoimmune disease, although the nature of the autoantigen has remained elusive. We propose that in auto e disease including MS, there is an unchecked amplification of T cells in vivo. These cells are dividing and therefore selectively enriched by the hprt mutant clonal assay. This assay will provide a method to identify and study T cells that are representative of clones dividing in vivo. Our preliminary data has shown that the hprt mutant frequency is increased in a number of autoimmune diseases, including MS. Furthermore, five or six MS patients have hprt mutant T cells that show reactivity to myelin basic protein while wild type clones do not. Our overall objective is to study the mutant frequency in patients over time, and determine the extent of this antigen reactivity in the MS population, and define the fine specificity and T cell receptor gene usage in these clones.